MAP3K12

This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.

Full Name

MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 12

Function

Part of a non-canonical MAPK signaling pathway (PubMed:28111074).
Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074).
May be an activator of the JNK/SAPK pathway.

Biological Process

Histone phosphorylationISS:UniProtKB
Intracellular signal transductionManual Assertion Based On ExperimentTAS:ProtInc
JNK cascadeBy SimilarityISS:UniProtKB
Negative regulation of motor neuron apoptotic processIEA:Ensembl
Peptidyl-serine phosphorylationISS:UniProtKB
Peptidyl-threonine phosphorylationISS:UniProtKB
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JUN kinase activityISS:ARUK-UCL
Positive regulation of protein kinase activityISS:ARUK-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:UniProtKB
Protein autophosphorylationBy SimilarityISS:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB

PTM

Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated (By similarity).
The activity of MAP3K12 can be regulated through its proteasomal degradation. APOE, through a receptor-mediated mechanism, activates MAP3K12 by preventing its proteasomal degradation.